The objectives of this research program are twofold: 1) to determine the mechanisms by which N. gonorrhoeae causes disease and 2) to determine methods for blocking those pathogenic mechanisms. The Principal Investigator and colleagues have developed various experimental models which use human fallopian tubes in organ culture to quantitate the rate of damage to genital mucosa by gonococci, the degree of attachment to genital mucosa by gonoccoci, and the extent of entry of gonococci into cells of genital mucosa. Studies will be performed to further identify a filterable toxic factor or factors that are present in supernatant fluid from gonococcal-infected organ cultures and that damage human fallopian tube mucosa. Gonococcal lipopolysaccharide, which has been shown in our laboratory to damage the fallopian tube mucosa, will be separated into its major components, lipid A, core polysaccharide, and available side chains, to determine which is responsible for damage and which is the antigenic moiety. Antibodies directed against gonococcal pili, lipopolysaccharide, outer membrane protein, and outer membrane complex will be tested for their ability to block attachment to or damage of human fallopian tube mucosa by whole gonococci and their toxic components. We have shown that cells of the fallopian tube mucosa phagocytize gonococci and transport them, morphologically intact, to the submucosa. Since some candidate components of a future gonococcal vaccine elicit opsonic antibody to gonococci, we will determine if the gonococci inside the mucosal cells are viable and if the vaccine-induced opsonic antibodies enhance tissue invasion by gonococci. Other studies will be aimed at verifying our observations of apparent capsular material on gonococci in urethral exudate using an electron-microscopic India ink technique. We believe that a better understanding of the pathogenic mechanisms of gonococci and factors which block those mechanisms is critical in the effort to produce an effective gonococcal vaccine.